Search

Background Human African trypanosomiasis (HAT) is a neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by tsetse flies in sub-Saharan West Africa. In southern Chad the most active and persistent focus is the Mandoul focus, with 98% of the reported human cases, and where African animal trypanosomosis (AAT) is also present. Recently, a control project to eliminate tsetse flies (Glossina fuscipes fuscipes) in this focus using the sterile insect technique (SIT) was initiated. However, the release of large numbers of sterile males of G. f. fuscipes might result in a potential temporary increase in transmission of trypanosomes since male tsetse flies are also able to transmit the parasite. The objective of this work was therefore to experimentally assess the vector competence of sterile males treated with isometamidium for Trypanosoma brucei brucei. Methods An experimental infection was set up in the laboratory, mimicking field conditions: the same tsetse species that is present in Mandoul was used. A T. b. brucei strain close to T. b. gambiense was used, and the ability of the sterile male tsetse flies fed on blood with and without a trypanocide to acquire and transmit trypanosomes was measured. Results Only 2% of the experimentally infected flies developed an immature infection (midgut) while none of the flies developed a metacyclic infection of T. b. brucei in the salivary glands. We did not observe any effect of the trypanocide used (isometamidium chloride at 100 mg/l) on the development of infection in the flies. Conclusions Our results indicate that sterile males of the tested strain of G. f. fuscipes were unable to cyclically transmit T. b. brucei and might even be refractory to the infection. The data of the research indicate that the risk of cyclical transmission of T. brucei by sterile male G. f. fuscipes of the strain colonized at IAEA for almost 40 years appears to be small. Graphical Abstract

All raw sequence read data are available from the European Nucleotide Archive under the accession number PRJEB49793: https://www.ebi.ac.uk/ena/browser/view/PRJEB49793. Sample data set, sample metadata, and codes for analysis are available on GitHub: https://github.com/wouterhendrycks/tephritid_microbiome_host_switch_project and in Zenodo: https://doi.org/10.5281/zenodo.6810766.Supporting Information table (Differential abundance analysis of bacterial genera between larval microbiomes from larvae between different host plants and between different sites using ALDEx2) is available in the Zenodo repository at https://doi.org/10.5281/zenodo.6811204).; International audience; Graphical Abstract:We investigated how the gut microbiome composition changes in a cucurbit-feeding fly Zeugodacus cucurbitae when it feeds on atypical solanaceous hosts instead of typical cucurbit hosts. Wild parental (F0) adults and semiwild first filial (F1) larvae of Z. cucurbitae collected from two locations in Réunion Island showed heterogeneous microbiome responses across host plants. This study shows how local processes and host plants can strongly affect the composition of the insect microbiome and the importance of using adequately sampled populations. Figure: https://onlinelibrary.wiley.com/cms/asset/10ec8f92-c6b0-4f27-aaf0-0ed246f23aa9/mbo31307-gra-0001-m.jpgAbstract: While contemporary changes in feeding preferences have been documented in phytophagous insects, the mechanisms behind these processes remain to be fully clarified. In this context, the insect gut microbiome plays a central role in adaptation to novel host plants. The cucurbit frugivorous fruit fly Zeugodacus cucurbitae (Diptera, Tephritidae) has occasionally been reported on "unconventional" host plants from different families, including Solanaceae. In this study, we focus on wild parental (F-0) adults and semiwild first filial (F-1) larvae of Z. cucurbitae from multiple sites in La Reunion and explore how the gut microbiome composition changes when this fly is feeding on a noncucurbit host (Solanum melongena). Our analyses show nonobvious gut microbiome responses following the F-0-F-1 host shift and the importance of not just diet but also local effects, which heavily affected the diversity and composition of microbiomes. We identified the main bacterial genera responsible for differences between treatments. These data further stress the importance of a careful approach when drawing general conclusions based on laboratory populations or inadequately replicated field samples.

Background African animal trypanosomosis (AAT), transmitted by tsetse flies, is arguably the main disease constraint to integrated crop-livestock agriculture in sub-Saharan Africa, and African heads of state and governments adopted a resolution to rid the continent of this scourge. In order to sustainably reduce or eliminate the burden of AAT, a progressive and evidence-based approach is needed, which must hinge on harmonized, spatially explicit information on the occurrence of AAT and its vectors. Methods A digital repository was assembled, containing tsetse and AAT data collected in Burkina Faso between 1990 and 2019. Data were collected either in the framework of control activities or for research purposes. Data were systematically verified, harmonized, georeferenced and integrated into a database (PostgreSQL). Entomological data on tsetse were mapped at the level of individual monitoring traps. When this was not possible, mapping was done at the level of site or location. Epidemiological data on AAT were mapped at the level of location or village. Results Entomological data showed the presence of four tsetse species in Burkina Faso. Glossina tachinoides, present from the eastern to the western part of the country, was the most widespread and abundant species (56.35% of the catches). Glossina palpalis gambiensis was the second most abundant species (35.56%), and it was mainly found in the west. Glossina morsitans submorsitans was found at lower densities (6.51%), with a patchy distribution in the southern parts of the country. A single cluster of G. medicorum was detected (less than 0.25%), located in the south-west. Unidentified tsetse flies accounted for 1.33%. For the AAT component, data for 54,948 animal blood samples were assembled from 218 geographic locations. The samples were tested with a variety of diagnostic methods. AAT was found in all surveyed departments, including the tsetse-free areas in the north. Trypanosoma vivax and T. congolense infections were the dominant ones, with a prevalence of 5.19 ± 18.97% and 6.11 ± 21.56%, respectively. Trypanosoma brucei infections were detected at a much lower rate (0.00 ± 0.10%). Conclusions The atlas provides a synoptic view of the available information on tsetse and AAT distribution in Burkina Faso. Data are very scanty for most of the tsetse-free areas in the northern part of the country. Despite this limitation, this study generated a robust tool for targeting future surveillance and control activities. The development of the atlas also strengthened the collaboration between the different institutions involved in tsetse and AAT research and control in Burkina Faso, which will be crucial for future updates and the sustainability of the initiative. Graphical Abstract

International audience

International audience; tSheeppox (SPP) is a highly contagious disease of small ruminants caused by sheeppox virus (SPPV) and predominantly occurs in Asia and Africa with significant economic losses. SPPV is genetically and immunologically closely related to goatpox virus (GTPV) and lumpy skin disease virus (LSDV), which infect goats and cattle respectively. SPPV live attenuated vaccines (LAVs) are used for vaccination against SPP and goatpox (GTP). Mechanisms related to innate immunity elicited by SPPV are unknown. Although adaptive immunity is responsible for long-term immunity, it is the innate responses that prevent viral invasion and replication before LAVs generate specific long-term protection. We analyzed the relative expression of thirteen selected genes that included pattern recognition receptors (PRRs), Nuclear factor-kappa beta p65 (NF-kappa beta), and cytokines to understand better the interaction between SPPV and its host. The transcripts of targeted genes in sheep PBMC incubated with either wild type (WT) or LAV SPPV were analyzed using quantitative PCR. Among PRRs, we observed a significantly higher expression of RIG-1 in PBMC incubated with both WT and LAV, with the former producing the highest expression level. However, there was high inter-individual variability in cytokine transcripts levels among different donors, with the expression of TNF alpha, IL-15, and IL-10 all significantly higher in both PBMC infected with either WT or LAV compared to control PBMC. Correlation studies revealed a strong significant correlation between RIG-1 and IL-10, between TLR4, TNF alpha, and NF-kappa beta, between IL-18 and IL-15, and between NF-kappa beta and IL-10. There was also a significant negative correlation between RIG-1 and IFN gamma, between TLR3 and IL-1 beta, and between TLR4 and IL-15 (P< 0.05). This study identified RIG-1 as an important PRR in the signaling pathway of innate immune activation during SPPV infection, possibly through intermediate viral dsRNA. The role of immunomodulatory molecules produced by SPPV capable of inhibiting downstream signaling activation following RIG-1 upregulation is discussed. These findings advance our knowledge of the induction of immune responses by SPPV and will help develop safer and more potent vaccines against SPP and GTP.

International audience; Lumpy skin disease (LSD), an economically significant disease in cattle caused by lumpy skin disease virus (LSDV), is endemic to nearly all of Africa. Since 2012, LSDV has emerged as a significant epizootic pathogen given its rapid spread into new geographical locations outside Africa, including the Middle East, Eastern Europe, and Asia. To assess the genetic diversity of LSDVs in East Africa, we sequenced and analyzed the RPO30 and GPCR genes of LSDV in twenty-two archive samples collected in Ethiopia, Kenya, and Sudan before the appearance of LSD in the Middle East and its incursion into Europe. We compared them to publicly available sequences of LSDVs from the same region and those collected elsewhere. The results showed that the East African field isolates in this study were remarkably similar to each other and to previously sequenced field isolates of LSDV for the RPO30 and GPCR genes. The only exception was LSDV Embu/B338/2011, a field virus collected in Kenya, which displayed mixed features between the LSDV Neethling vaccine and field isolates. LSDV Embu/B338/2011 had the same 12-nucleotide insertion found in LSDV Neethling and KS-1 vaccines. Further analysis of the partial EEV glycoprotein, B22R, RNA helicase, virion core protein, NTPase, and N1R/p28-like protein genes showed that LSDV Embu/B338/2011 differs from previously described LSDV variants carrying the 12-nucleotide insertion in the GPCR gene. These findings highlight the importance of the constant monitoring of genetic variation among LSDV isolates.

Background Glossina austeni and Glossina brevipalpis (Diptera: Glossinidae) are the sole cyclical vectors of African trypanosomes in South Africa, Eswatini and southern Mozambique. These populations represent the southernmost distribution of tsetse flies on the African continent. Accurate knowledge of infested areas is a prerequisite to develop and implement efficient and cost-effective control strategies, and distribution models may reduce large-scale, extensive entomological surveys that are time consuming and expensive. The objective was to develop a MaxEnt species distribution model and habitat suitability maps for the southern tsetse belt of South Africa, Eswatini and southern Mozambique. Methodology/Principal findings The present study used existing entomological survey data of G. austeni and G. brevipalpis to develop a MaxEnt species distribution model and habitat suitability maps. Distribution models and a checkerboard analysis indicated an overlapping presence of the two species and the most suitable habitat for both species were protected areas and the coastal strip in KwaZulu-Natal Province, South Africa and Maputo Province, Mozambique. The predicted presence extents, to a small degree, into communal farming areas adjacent to the protected areas and coastline, especially in the Matutuíne District of Mozambique. The quality of the MaxEnt model was assessed using an independent data set and indicated good performance with high predictive power (AUC > 0.80 for both species). Conclusions/Significance The models indicated that cattle density, land surface temperature and protected areas, in relation with vegetation are the main factors contributing to the distribution of the two tsetse species in the area. Changes in the climate, agricultural practices and land-use have had a significant and rapid impact on tsetse abundance in the area. The model predicted low habitat suitability in the Gaza and Inhambane Provinces of Mozambique, i.e., the area north of the Matutuíne District. This might indicate that the southern tsetse population is isolated from the main tsetse belt in the north of Mozambique. The updated distribution models will be useful for planning tsetse and trypanosomosis interventions in the area., Author summary The two tsetse species transmitting nagana in South Africa, Eswatini and southern Mozambique represent the southernmost distribution of this genus on the African continent. Distribution models were developed to support tsetse control. These models indicated that the main factors contributing to tsetse distribution in the area are the presence of host animals, variation in climate and vegetation mostly observed in protected areas, agricultural practises and land-use also had a significant and rapid impact on tsetse abundance in the area. Application of the model to areas north of the southern distribution predict a low presence of suitable habitats in the Gaza and Inhambane Provinces of Mozambique, thereby indicating that this southern population is geographically isolated from the main tsetse belt starting in the north of Mozambique.

International audience; This article is an oGoatpox virus (GTPV) belongs to the genus Capripoxvirus, together with sheeppox virus (SPPV) and lumpy skin disease virus (LSDV). GTPV primarily affects sheep, goats and some wild ruminants. Although GTPV is only present in Africa and Asia, the recent spread of LSDV in Europe and Asia shows capripoxviruses could escape their traditional geographical regions to cause severe outbreaks in new areas. Therefore, it is crucial to develop effective source tracing of capripoxvirus infections. Earlier, conventional phylogenetic methods, based on limited samples, identified three different nucleotide sequence profiles in the G-protein-coupled chemokine receptor (GPCR) gene of GTPVs. However, this method did not differentiate GTPV strains by their geographical origins. We have sequenced the GPCR gene of additional GTPVs and analyzed them with publicly available sequences, using conventional alignment-based methods and an alignment-free approach exploiting k-mer frequencies. Using the alignment-free method, we can now classify GTPVs based on their geographical origin: African GTPVs and Asian GTPVs, which further split into Western and Central Asian (WCA) GTPVs and Eastern and Southern Asian (ESA) GTPVs. This approach will help determine the source of introduction in GTPV emergence in disease-free regions and detect the importation of additional strains in disease-endemic areas

International audience; In 2005, the Government of Senegal initiated a project entitled "Projet de lutte contre les glossines dans les Niayes" (Tsetse control project in the Niayes) with the aim of creating a zone free of Glossina palpalis gambiensis in that area. The project received technical and financial support from the International Atomic Energy Agency (IAEA), the Food and Agriculture Organization of the United Nations (FAO), the Centre de Cooperation Internationale en Recherche Agronomique pour le Developpement (CIRAD) and the US Department of State through the Peaceful Uses Initiative (PUI). It was implemented in the context of the Pan African Tsetse and Trypanosomosis Eradication Campaign (PATTEC) following a phased conditional approach (PCA) that entails implementation in distinct phases, in which support to the next phase is conditional upon completion of all (or at least the majority of) activities in the previous phase. In the case of the tsetse project in Senegal, the PCA consisted of 4 phases: (1) commitment of all stakeholders and training, (2) baseline data collection, feasibility studies and strategy development, (3) preparatory pre-operational activities and (4) operational activities. This paper provides an overview of the main activities that were carried out within each phase, with emphasis on the operational research carried out in phases 2 and 3, that was instrumental in guiding the project's decision-making. Activities of phase 2 focused on the collection of entomological, veterinary, socio-economic and environmental baseline data, and a population genetics study that proved the isolated character of the G. p. gambiensis population of the Niayes. These data enabled the tsetse-infested area to be delimited to 1000 km(2), the impact of animal trypanosomosis on the farmers' welfare to be quantified (annual benefits of 2 million Euro in the tsetse-infested zone), and the formulation of an area-wide integrated pest management (AW-IPM) strategy that included a sterile insect (SIT) component to eradicate the isolated tsetse populations from the Niayes. In view of the extreme fragmentation of the remaining favourable habitat of the Niayes and the high human population density (peri-urban area), which excluded the possibility of using the Sequential Aerosol Technique, the IPM strategy that was selected comprised the suppression of the tsetse population with insecticide-impregnated traps/targets and the use of "pour-on" for cattle, followed by the release of sterile males to eliminate the remaining relic pockets. During phase 3, the pre-operational phase, a series of activities were carried out that were needed to implement the operational phase. These included the establishment of a colony of tsetse originating from the target area in Senegal, competitiveness studies between the sterile flies and those from the target area, development of transport methods for long-distance shipments of sterile male pupae, competitiveness of the sterile male flies after release in the target area, development of aerial release methods (including a new chilled adult release system) and development of a Maxent-based distribution model to guide the suppression, sterile male releases and monitoring of the eradication campaign. To be able to properly manage the eradication campaign in different phases, the entire target area was divided into 3 operational blocks. This paper demonstrates how, during the operational phase, scientific principles continued to guide the implementation process. The results to date are encouraging, i.e. the deployment of 269 insecticide-impregnated Vavoua traps in favourable habitat of Block 1 reduced the apparent density of the G. p. gambiensis population significantly (from 0.42 (SD 0.39) to 0.04 (SD 0.11) flies/trap/day). This was followed by the aerial release of sterile males that reduced the apparent density to zero after six months of releases. The last wild fly was trapped on August 9, 2012 in Block 1. In Block 2, during the suppression, the apparent fly density dropped from 1.24 (SD 1.23) to 0.005 (SD 0.017) flies/trap/day. Sterile male releases were initiated in February 2014 and expanded to cover the entire Block 2 in January 2015. The apparent fly density has so far been reduced to < 0.001 fly per trap per day until the end of 2018 and releases are still ongoing. The results of the campaign are discussed with respect to the "adaptive management approach" used, which was deemed critical for the success of the campaign.

International audience; African swine fever (ASF) has been endemic in sub-Saharan Africa since the 1960s. Following its introduction in Senegal, in 1957, ASF steadily progressed through West Africa, reaching Burkina Faso in 2003, and later Mali in 2016. Despite the heavy burden of disease on pig production, little information is available on the genetic diversity of Africa swine fever virus (ASFV) in Burkina Faso, Mali and Senegal. Here, we used real-time PCR ASFV to detect the ASFV genome in samples collected between 1989 and 2016, in Burkina Faso, Mali and Senegal, and conventional approaches for isolate characterization. The C-terminal end of the p72 protein gene, the full E183L gene and the central variable region (CVR) within the B602L gene in ASFV genome were sequenced and compared to publicly available sequences. ASFV genome was found in 27 samples, 19 from Burkina Faso, three from Mali and five from Senegal. The phylogenetic analyses showed that all viruses belong to genotype I, with the ASFVs from Burkina Faso and Mali grouping with genotype Ia and ASFV serogroup 4, and those from Senegal with genotype Ib and the ASFV serogroup 1. The analysis of the CVR tetrameric tandem repeat sequences (TRS) showed four TRS variants in Burkina Faso, two in Senegal and one in Mali. The three countries did not share any common TRS, and all CVRs of this study differed from previously reported CVRs in West Africa, except for Senegal. Three of the five isolates from Senegal fully matched with the CVR, p72 and p54 sequences from ASFV IC96 collected during the 1996 ASF outbreak in Ivory Coast. This study shows the spread of the same ASFV strains across countries, highlighting the importance of continuous m;onitoring of ASFV isolates. It also calls for an urgent need to establish a regional plan for the control and eradication of ASF in West Africa

International audience; 1. Tsetse flies (Diptera: Glossinidae) are K‐strategist species and deposit a single larva at 10‐day intervals in specific sites. As larviposition site selection strongly impacts reproductive success, the selection of larviposition sites is unlikely to be random and will be subject to strong selective processes, probably mediated by specific cues.2. This study was designed to assess the existence of an aggregation effect in the palpalis group and to test its potential chemical nature (contact or volatile compounds). The larviposition site selection of Glossina palpalis gambiensis was studied according to the presence of conspecific and heterospecific larvae (morsitans group) buried in substrates. Three sets of experiments were performed with either individual or grouped gravid females and with or without physical access to the substrate.3. In individual larviposition experiments, females were more likely to select trays with buried larvae than unconditioned sand (63.2% and 36.8%, respectively; P

Small ruminants (e.g., sheep and goats) contribute considerably to the cash income and nutrition of small farmers in most countries in Africa and Asia. Their husbandry is threatened by the highly infectious transboundary viral disease peste des petits ruminants (PPR) caused by peste-des-petits-ruminants virus (PPRV). Given its social and economic impact, PPR is presently being targeted by international organizations for global eradication by 2030. Since its first description in Côte d’Ivoire in 1942, and particularly over the last 10 years, a large amount of molecular epidemiological data on the virus have been generated in Africa. This review aims to consolidate these data in order to have a clearer picture of the current PPR situation in Africa, which will, in turn, assist authorities in global eradication attempts. Electronic supplementary material The online version of this article (10.1007/s00705-020-04732-1) contains supplementary material, which is available to authorized users.

Growing evidence suggests that multiple wildlife species can be infected with peste des petits ruminants virus (PPRV), with important consequences for the potential maintenance of PPRV in communities of susceptible hosts, and the threat that PPRV may pose to the conservation of wildlife populations and resilience of ecosystems. Significant knowledge gaps in the epidemiology of PPRV across the ruminant community (wildlife and domestic), and the understanding of infection in wildlife and other atypical host species groups (e.g., camelidae, suidae, and bovinae) hinder our ability to apply necessary integrated disease control and management interventions at the wildlife-livestock interface. Similarly, knowledge gaps limit the inclusion of wildlife in the FAO/OIE Global Strategy for the Control and Eradication of PPR, and the framework of activities in the PPR Global Eradication Programme that lays the foundation for eradicating PPR through national and regional efforts. This article reports on the first international meeting on, “Controlling PPR at the livestock-wildlife interface,” held in Rome, Italy, March 27–29, 2019. A large group representing national and international institutions discussed recent advances in our understanding of PPRV in wildlife, identified knowledge gaps and research priorities, and formulated recommendations. The need for a better understanding of PPRV epidemiology at the wildlife-livestock interface to support the integration of wildlife into PPR eradication efforts was highlighted by meeting participants along with the reminder that PPR eradication and wildlife conservation need not be viewed as competing priorities, but instead constitute two requisites of healthy socio-ecological systems.

Contagious bovine pleuropneumonia (CBPP) and contagious caprine pleuropneumonia (CCPP) are major infectious diseases of ruminants caused by mycoplasmas in Africa and Asia. In contrast with the limited pathology in the respiratory tract of humans infected with mycoplasmas, CBPP and CCPP are devastating diseases associated with high morbidity and mortality. Beyond their obvious impact on animal health, CBPP and CCPP negatively impact the livelihood and wellbeing of a substantial proportion of livestock-dependent people affecting their culture, economy, trade and nutrition. The causative agents of CBPP and CCPP are Mycoplasma mycoides subspecies mycoides and Mycoplasma capricolum subspecies capripneumoniae, respectively, which have been eradicated in most of the developed world. The current vaccines used for disease control consist of a live attenuated CBPP vaccine and a bacterin vaccine for CCPP, which were developed in the 1960s and 1980s, respectively. Both of these vaccines have many limitations, so better vaccines are urgently needed to improve disease control. In this article the research community prioritized biomedical research needs related to challenge models, rational vaccine design and protective immune responses. Therefore, we scrutinized the current vaccines as well as the challenge-, pathogenicity- and immunity models. We highlight research gaps and provide recommendations towards developing safer and more efficacious vaccines against CBPP and CCPP.

Background: Tsetse flies transmit trypanosomes that cause the debilitating diseases human African trypanosomosis (HAT) or sleeping sickness in humans and animal African trypanosomosis (AAT) or nagana in livestock. The riverine tsetse species Glossina palpalis gambiensis Vanderplank (Diptera: Glossinidae) inhabits riparian forests along river systems in West Africa. The Government of Senegal has embarked on a project to eliminate a population of this tsetse species from the Niayes area with the objective to manage AAT in the area. The project is implemented following an area-wide integrated pest management approach with an SIT component. The SIT can only be successful when the sterile males that are released in the field are of high biological quality, i.e. have the same dispersal capacity, survival and competitiveness as their wild counterparts. To date, sterile tsetse males have been released by air using biodegradable cardboard cartons that were manually dropped from a fixed-wing aircraft or gyrocopter. The cardboard boxes are however expensive, and the system is rather cumbersome to implement. Methods: A new prototype of an automated chilled adult release system (Bruno Spreader Innovation, (BSI™)) for tsetse flies was tested for its accuracy (in counting numbers of sterile males as loaded into the machine), release rate consistency and impact on quality of the released males. The impact of the release process was evaluated on several performance indicators of the irradiated male flies such as flight propensity, survival, mating competitiveness, premating and mating duration, and insemination rate of mated females. Results: The BSI TM release system counted with a consistent accuracy and released homogenously tsetse flies at the lowest motor speed (0.6 rpm). In addition, the chilling conditions (6 ± 1 o C) and the release process (passing of flies through the machine) had no significant negative impact on the males' flight propensity. No significant differences were observed between the control males (no irradiation and no exposure to the release process), irradiated males (no exposure to the release process) and irradiated males exposed to the release process with respect to mating competitiveness, premating period and mating duration. Only survival of irradiated males that were exposed to the release process was reduced, irrespective of whether the males were held with or without feeding. Conclusion: Although the release process had a negative effect on survival of the flies, the data of the experiments indicate that the BSI machine holds promise for use in operational tsetse SIT programmes. The promising results of this study will now need to be confirmed under operational field conditions in West Africa.

1Insect Pest Control Laboratory, Joint FAO/IAEA Programme of Nuclear Techniques in Food and Agriculture, Vienna, Austria, 2Ministry of Agriculture, Natural Resourcesand Environment, Zanzibar, Tanzania, 3Vector and Vector Borne Diseases Research Institute, Tanga, Tanzania, 4Insect Pest Control Section, Joint FAO/IAEA Programme ofNuclear Techniques in Food and Agriculture, Vienna, Austria, 5Retired, Independent Researcher, Vienna, Austria, 6Livestock Research, Training & Extension, Ministry ofLivestock & Fisheries Development, Dar es Salaam, Tanzania, 7Unite´ Mixte de Recherche Controˆle des Maladies Animales Exotiques et Emergentes, Centre de Coope´rationInternationale en Recherche Agronomique pour le De´veloppement (CIRAD), Montpellier, France, 8Unite´ Mixte de Recherche 1309 Controˆle des Maladies AnimalesExotiques et Emergentes, Institut national de la recherche agronomique (INRA), Montpellier, France, 9Institut Se´ne´galais de Recherches Agricoles, Laboratoire Nationald’Elevage et de Recherches Ve´te´rinaires, Dakar-Hann, Se´ne´gal

Type I interferons (IFN-I) are important cytokines linking innate and adaptive immunity. Plasmacytoid dendritic cells make high levels of IFN-I in response to viral infection and are thought to be the major source of the cytokines in vivo. Here, we show that conventional non-plasmacytoid dendritic cells taken from mice infected with a dendritic-cell-tropic strain of lymphocytic choriomeningitis virus make similarly high levels of IFN-I on subsequent culture. Similarly, non-plasmacytoid dendritic cells secrete high levels of IFN-I in response to double-stranded RNA (dsRNA), a major viral signature, when the latter is introduced into the cytoplasm to mimic direct viral infection. This response is partially dependent on the cytosolic dsRNA-binding enzyme protein kinase R and does not require signalling through toll-like receptor (TLR) 3, a surface receptor for dsRNA. Furthermore, we show that sequestration of dsRNA by viral NS1 (refs 6, 7) explains the inability of conventional dendritic cells to produce IFN-I on infection with influenza. Our results suggest that multiple dendritic cell types, not just plasmacytoid cells, can act as specialized interferon-producing cells in certain viral infections, and reveal the existence of a TLR-independent pathway for dendritic cell activation that can be the target of viral interference.